合成路线1

A new total synthesis of racemic epibatidine has been reported: The benzoylation of trans-4-aminocyclohexanol (I) with benzoyl chloride gives the benzamide (II), which is treated with methanesulfonyl chloride and triethylamine to yield the mesylate (III). Cyclization of (III) by means of potassium tert-butoxide in DMF/benzene affords the 7-azanorbornane (IV), which by microbial hydroxylation using the fungus Beauveria bassiana gives stereoselectively the endo-2-hydroxy-7-azanorbornane (V). Oxidation of (V) with TPAP and NMO in dichloromethane yields the ketone (VI), which is condensed with 2-chloro-5-iodopyridine (VII) by means of butyllithium in THF affording exclusively the endo-alcohol (VIII). Reaction of (VIII) with methoxalyl chloride (IX) and DMAP/2,6-lutidine in dichloromethane gives the mixed oxalate (IX), which is reduced with tributyltin hydride and AIBN to yield exclusively the endo-isomer (XI). Isomerization of (XI) by means of potassium tert-butoxide in refluxing tert-butanol affords the exo-isomer (XII), which is finally debenzoylated by treatment with 6N HCl at 100 C.